Ubiquitin Specific Protease 9X Regulates the Activation of ARK5 and Promotes Progression of Fibrotic Remodeling
USP9X plays a crucial role in myocardial fibrosis. This study showed increased USP9X expression in myocardial infarction models, associated with collagen deposition and myofibroblast activation. Myofibroblast-specific USP9X knockout and pharmacologic inhibition with Degrasyn both reduced fibrosis and improved cardiac function. Mechanistically, USP9X was found to bind and deubiquitinate AMPK-related kinase 5, thereby activating it and promoting transforming growth factor-β1-induced myofibroblast transformation via the Rho kinase pathway. These findings highlight USP9X as a potential therapeutic target for fibrotic diseases.
Authors
- Xiaopeng Guo (ORCID: https://orcid.org/0000-0002-2274-0929)
- Steve Jiang (ORCID: https://orcid.org/0000-0002-3083-6752)
- Yumiao Wei (ORCID: https://orcid.org/0000-0001-8106-9218)
- Wenling Yang (ORCID: https://orcid.org/0000-0002-6348-7747)
- Xuelian Li (ORCID: https://orcid.org/0000-0001-9043-8580)
- Fan Zhang (ORCID: https://orcid.org/0000-0002-2715-5657)
- Xiangyu Zhu (ORCID: https://orcid.org/0000-0001-7787-2550)
- Zhiyang Li (ORCID: https://orcid.org/0000-0002-8928-7671)
Institutions
- Army Medical University (CN)
- Dalian Medical University (CN)
- Wuhan Union Hospital (CN)
- Southwest Hospital (CN)
- Union Hospital (CN)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1016/j.jacbts.2025.02.014
- Citations
- 2
- Primary Topic
- Protease and Inhibitor Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.87
Funders
- National Natural Science Foundation of China